18.1Introduction

The pancreas is a compound tubular-alveolar gland composed of an exocrine portion (serous acini) and an endocrine portion (islets of Langerhans). The islet cells make up only 1% of the total pancreatic mass.

Chronic inflammation of the salivary and lacrimal glands in Sjögren’s syndrome (SjS) results in xerostomia and keratoconjunctivitis sicca in 95% of patients [1]. The pancreas, an exocrine gland with some functional, anatomical, and histological similarities to salivary glands, has been thought to be involved in SjS. Investigators have assessed pancreatic involvement of SjS by analyzing the histopathological changes, evaluating the pancreatic endocrine and exocrine function, interrogating specific pancreatic antibodies, and applying radiological techniques such as endoscopic retrograde cholangiopancreatography (ERCP), computed tomography, and ultrasonography. There still remains significant uncertainty regarding the true prevalence of pancreatic involvement in SjS, largely because of the realization recently that substantial overlap exists between SjS and IgG4-related disease (IgG4-RD).

18.2The Overlap Between SjS and IgG4-Related Disease

The concept of chronic pancreatitis associated with or caused by an autoimmune mechanism was outlined first in the early 1960s [2–5]. In 1975, Waldram et al. [6] described what they believed to be a new syndrome of chronic pancreatitis, sclerosing cholangitis, and sicca complex in two siblings. A subsequent case with pancreas and salivary gland involvement was reported by Sjögren et al. [7] in 1979. Those authors indicated that this syndrome might represent a distinct disease entity with a common pathogenic mechanism. Subsequent reports alluded to the coexistence of SjS with pancreatitis, pulmonary infiltrates or fibrosis, retroperitoneal fibrosis, sclerosing cholangitis, and pancreatic pseudotumors [8–11]. Successful glucocorticoid therapy for pancreatitis associated with SjS was documented in 1976 [12].

In 1995, the concept of autoimmune pancreatitis (AIP) was introduced to the medical literature [13] and as the knowledge about this condition grew, it was realized that many of the cases previously regarded as SjS are actually part of the IgG4-RD spectrum. It is worth noting that the association of SjS with fibroinflammatory manifestations has not been reported since the recognition of IgG4-RD. One can justifiably speculate that many of the reported cases of pancreatitis cases in patients with SjS had IgG4-related sialadenitis and not SjS.

Most studies evaluating patients with SjS have included some cases of IgG4related sialadenitis with negative Sjögren’s autoantibodies. Consequently, the literature on “SjS” and pancreatitis is riddled with potential inaccuracies and interpreting the true association between SjS and pancreatitis is complex. Table 18.1 summarizes the characteristics that help distinguish SjS from IgG4-related sialadenitis and IgG4-related dacryoadenitis.